autism
Definition: Autism is a neurodevelopmental syndrome defined by deficits in social reciprocity and communication and by unusual repetitive behaviors. Although there is an underlying genetic predisposition, the etiology of autism is currently unknown. A recent increase in prevalence suggests that genetically determined vulnerability to environmental exposure might contribute to the causation of autism.
Autism is a common and genetically heterogeneous disorder, with an estimated heritability of >90%.
Its specific underlying causes are largely unknown. Here, I propose that low levels of autistic vulnerability, reflected in social-cognitive processing differences, do not necessarily manifest in a behavioural phenotype but are usually compensated for during development.
They are more likely to lead to a recognizable syndrome among individuals of low intelligence, who are male or have independent neurodevelopmental vulnerability owing to a wide range of gene mutations, chromosomal anomalies or environmental insults.
Consequently, the apparent association between mental retardation and autistic syndromes is not because they usually have common causes, but rather because the presence of both features greatly increases the probability of clinical ascertainment.
Susceptibility loci
1q21-22
3q25-27 (#12192642#)
7q21-q36 (Target gene: reelin) (#16311013#)
15q11-q13 (#12567325#)
17q11 (in males) (#15467983#)
17q21 (#15806440#, #15877280#)
GABA receptor subunit genes
Gene variants
GLO1 variants
MTF1 (rs3790625, P = .02) (#15446388#)
SLC11A3 (rs2304704, P = .07) (#15446388#)
Reviews
Skuse DH. Rethinking the nature of genetic vulnerability to autistic spectrum disorders. Trends Genet. 2007 Aug;23(8):387-95. PMID: #17630015#
Thornalley PJ. Unease on the role of glyoxalase 1 in high-anxiety-related behaviour. Trends Mol Med. 2006 May;12(5):195-9. PMID: #16616641#
Folstein SE, Rosen-Sheidley B. Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet. 2001 Dec;2(12):943-55. PMID: #11733747#
Lamb JA, Moore J, Bailey A, Monaco AP. Autism: recent molecular genetic advances. Hum Mol Genet. 2000 Apr 12;9(6):861-8. PMID: #10767308#
References
Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J, Shago M, Moessner R, Pinto D, Ren Y, Thiruvahindrapduram B, Fiebig A, Schreiber S, Friedman J, Ketelaars CE, Vos YJ, Ficicioglu C, Kirkpatrick S, Nicolson R, Sloman L, Summers A, Gibbons CA, Teebi A, Chitayat D, Weksberg R, Thompson A, Vardy C, Crosbie V, Luscombe S, Baatjes R, Zwaigenbaum L, Roberts W, Fernandez B, Szatmari P, Scherer SW. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet. 2008 Feb;82(2):477-88. PMID: #18252227#
Jacquemont ML, Sanlaville D, Redon R, Raoul O, Cormier-Daire V, Lyonnet S, Amiel J, Le Merrer M, Heron D, de Blois MC, Prieur M, Vekemans M, Carter NP, Munnich A, Colleaux L, Philippe A. Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders. J Med Genet. 2006 Nov;43(11):843-9. PMID: #16840569#
Association of Reelin gene polymorphisms with autism. Serajee FJ, Zhong H, Mahbubul Huq AH. Genomics. 2006 Jan;87(1):75-83. PMID: #16311013#
Polymorphisms in xenobiotic metabolism genes and autism. Serajee FJ, Nabi R, Zhong H, Huq M. J Child Neurol. 2004 Jun;19(6):413-7. PMID: #15446388#